This invention relates to mass spectrometry. In particular, the invention relates to an ion beam guide apparatus, systems and method for use in mass spectrometry.
Mass spectrometry is an analytical methodology used for quantitative elemental analysis of materials and mixtures of materials. In mass spectrometry, a sample of a material to be analyzed, called an analyte, is broken into particles of its constituent parts and some of the particles are given an electric charge. Those particles, referred to hereinbelow as analyte ions, are typically molecular in size. Once produced, the analyte ions are separated by the spectrometer based on their respective masses. The separated analyte ions are then detected and a xe2x80x9cmass spectrumxe2x80x9d of the material is produced. The mass spectrum is analogous to a fingerprint of the sample material being analyzed. The mass spectrum provides information about the masses and in some cases the quantities of the various analyte particles that make up the sample. In particular, mass spectrometry can be used to determine the molecular weights of molecules and molecular fragments within an analyte. Additionally, mass spectrometry can identify components within the analyte based on the fragmentation pattern when the material is broken into particles. Mass spectrometry has proven to be a very powerful analytical tool in material science, chemistry and biology along with a number of other related fields.
Many forms of mass spectrometry produce analyte ions at relatively high pressures compared to the pressures extant in other portions of the mass spectrometer. For example, Atmospheric Pressure Matrix Assisted Laser Desorption Ionization (AP-MALDI), Field Asymmetric Ion Mobility Spectrometry (FAIMS), Atmospheric Pressure Ionization (API, including its subsets, such as Electrospray Ionization (ESI) and Atmospheric Pressure Chemical Ionization (APCI)), and Inductively Coupled Plasma (ICP) mass spectrometry, are a few forms of mass spectrometry using high pressures for ionization that are known in the art. All of these mass spectrometric methods generate ions at or near atmospheric pressure (760 Torr). Once generated, the analyte ions must be introduced or sampled into the mass spectrometer. Typically, the interior portions of a mass spectrometer are maintained at high vacuum levels ( less than 10xe2x88x924 Torr) or even ultra-high vacuum levels ( less than 10xe2x88x927 Torr). In practice, sampling the ions requires transporting the analyte ions in the form of a narrowly confined ion beam from the ion source to the high vacuum mass spectrometer chamber by way of one or more intermediate vacuum chambers. Each of the intermediate vacuum chambers is maintained at a vacuum level between that of the proceeding and following chambers. Therefore, the ion beam transporting the analyte ions transitions in a stepwise manner from the pressure levels associated with ion formation to those of the mass spectrometer.
At interfaces between each chamber, the ion beam passes from one chamber to the next through small apertures or orifices. The apertures are small enough that each of the intermediate vacuum chambers can maintain the desired vacuum level using a vacuum pump in spite of gas leakage that occurs between chambers at the aperture.
To be effective in mass spectrometer application, the ion beam must be able to transport the analyte ions through each of the intermediate vacuum chambers and into the mass spectrometer without significant loss of ions. Loss of ions typically occurs due to interaction with gas molecules inside the intermediate vacuum chambers. While the ion beam is passing through the intermediate vacuum chamber, analyte ions can and do collide with gas molecules present causing the ions to be slowed down or xe2x80x9cstalled outxe2x80x9d. Ions that are sufficiently slowed by this interaction will tend to drift to the walls of the intermediate vacuum chambers where they are xe2x80x9ctrappedxe2x80x9d and subsequently lost from the beam.
Even if significant ion loss does not occur, the interaction between analyte ions of the beam and gas molecules present in the intermediate vacuum chambers can also cause the beam to widen or to spread. If the beam is widened too much, the number of analyte ions that will ultimately pass through the aperture at an output end of the chamber will be reduced by an unacceptable amount. Therefore, ion beams that carry the analyte ions through intermediate vacuum chambers are generally transported using xe2x80x9cion guidesxe2x80x9d. The use of ion guides is primarily intended to minimize the loss of ions being transported and to control the ion beam volumetric and energy characteristics.
Ion guides are devices that utilize electromagnetic fields to confine the ions radially (x and y) while allowing or even promoting ion transport axially (z). Franzen, xe2x80x9cElectrical Ion Guidesxe2x80x9d, 1996 ASMS Conference Proceedings, p 1170 provides a short overview of the two principal types of electrical ion guides: the electrodynamic ion guides and the electrostatic ion guides. Electrodynamic ion guides employ repellent inhomogeneous radio frequency (RF) fields to create electric pseudo-potential wells to confine the analyte ions as they travel through the guide. Common electrodynamic type ion guides include for example, RF multipoles and ring stacks. Electrostatic ion guides utilize attracting forces around a thin wire or similar mechanism to control the motion of the analyte ions in the guide.
In addition to controlling the ion beam during transport, it is often necessary to reduce the phase space volume of the ion beam at certain points during transport. Phase space volume refers to a six dimensional space of x, y and z position and x, y and z momentum. An example of this is the need to reduce the beam diameter to maximize its transmission through small diameter apertures in the vacuum chamber interfaces. Beam diameter reduction may require xe2x80x9ccollisional focusingxe2x80x9d and/or xe2x80x9ccollisional coolingxe2x80x9d of the ion beam. Collisional focusing/cooling is generally accomplished with the ion guide at elevated pressures.
Collisional focusing is the use of repeated collisions of ions with neutral molecules in a suitably confining electromagnetic field, thereby reducing the radial position and/or energy of the beam. That is, the ions are focused into a smaller, more parallel beam. For more information about collision focusing see, for example, D. J. Douglas and J. B. French, xe2x80x9cCollision Focusing Effects in Radio Frequency Quadrupolesxe2x80x9d, J. Am. Soc. Mass Spectrom., 3 (1992) pp. 398-408.
Collisional cooling is the use of repeated collisions of ions with neutral molecules to retard the average axial energy of the ion beam and to narrow its distribution. In other words, the beam has a lower, more uniform axial energy. To a first order, the number of collisions an ion is subjected to is dependent on the xe2x80x9ccollision cross sectionxe2x80x9d of the ion and the xe2x80x9cgas thicknessxe2x80x9d. Collision cross section is the effective area for scattering or reaction between two specified particles. Gas thickness is the product of neutral gas density and ion path length.
Generally it takes considerably more collisions to focus a beam than to cool it. It takes higher neutral gas density or longer ion path length to focus or cool ions with small cross sections. And further, it takes more collisions to cool or focus ions with larger masses. Thus, a complicated situation may result where the neutral gas pressure that yields a gas thickness high enough to guarantee adequate cooling and/or focusing of all ions may be too high for many of the ions involved. In other words, some ions, particularly low mass ions, may be overly cooled and can become xe2x80x9ctrappedxe2x80x9d or have their axial velocities reduced below a practical or preferable level.
Also, it is sometimes desirable or even necessary to perform several stages of ionization with intermediate mass spectrometric stages, generically referred to as xe2x80x9cMS/MSxe2x80x9d. In one common implementation, called a xe2x80x9cTriple Quadxe2x80x9d, molecules are ionized (creating the xe2x80x9cparentxe2x80x9d ions), mass-filtered, fragmented (creating the xe2x80x9cdaughterxe2x80x9d ions) and mass-filtered again. The fragmentation takes place in a xe2x80x9ccollision cellxe2x80x9d. The collision cell is a chamber between adjacent mass spectrometers with significant gas thickness and energy to fragment the analyte ions through collisions with neutral gas particles within the fragmentation cell. The fragmentation in the collision cell requires the simultaneous confinement, transport, and focusing of both parent and daughter ions to the next mass spectrometer. The term xe2x80x9cparent ionxe2x80x9d refers to the analyte ion prior to fragmentation and the term xe2x80x9cdaughter ionxe2x80x9d refers to the resulting ions produced by the fragmentation. Since different ions will have different ionization cross sections, a pressure high enough to ensure fragmentation of all ions may lead to excessive cooling of lighter ions. On the other hand, very high axial energies (100 eV) may be required for fragmentation. If there is not significant subsequent cooling, the exiting beam may have a very broad distribution of axial energies leading to sub-optimal performance in the final mass spectrometer. Moreover, parent and daughter ions will have different cross sections and masses from each other that must be accommodated by the pressure chosen. All of these circumstances may require that the cell pressure be set higher than one might otherwise choose, causing some ions to stall out.
Thus, there is a need for devices that simultaneously transport, confine, focus and cool an ion beam while still maintaining sufficient axial energy. Such devices require adding axial energy, or accelerating the analyte ions, through an axial field. The addition of axial energy through an axial field must be achieved in such a manner that the axial energy is not high enough to cause fragmentation. There are many techniques known in the art to add axial energy through an axial field. U.S. Pat. No. 5,847,386 and the related PCT application no. WO 97/07530 of Thomson et al. describe some of these techniques and devices.
The RF multipole is one type of such devices described by Thompson et al. FIGS. 1A-1C illustrate various conventional RF multipoles. The RF multipoles require only two RF voltages, provide focusing and have an effective-potential well that can be tailored using multipole terms. FIG. 1A illustrates a conventional quadrupole while FIGS. 1B and 1C illustrate a hexapole and an octupole respectively. An RF voltage applied to the four axially oriented conductive rods that make up the quadrupole produces an inhomogeneous RF field between the rods. The magnitude of the field is greatest in the vicinity of the rods and minimum at a center point equal distance from the rods. The oscillation of the analyte ions in the presence of the RF field tends to move the ions down the RF gradient and towards the minimum field point or potential well. The movement of the ions along the gradient has given rise to the notion of a psuedo-potential force on the ions. See, for example, Tolmachev et al., xe2x80x9cA Collisional Focusing Ion Guide for Coupling an Atmospheric Pressure Ion Source to a Mass Spectrometerxe2x80x9d, Nucl. Instr. Meth. In Phys. Res., B 124 (1997) 112-119 and S. Guan and A. G. Marshall, xe2x80x9cStacked-Ring Electrostatic Ion Guidexe2x80x9d, J. Am. Soc. Mass Spectrom., 7 (1996) 101-106. However, the RF multipoles provide no intrinsic axial acceleration. To achieve axial acceleration, tapered or splayed rods; a voltage drop across resistive rods, resistive helper rods, or external rings; or axial segmentation of the multipoles may be used.
S. Guan and A. G. Marshall, cited supra, describe another device, the ring guide. FIG. 2 illustrates this alternative to the RF multipole ion guide also known as the conventional stacked-ring ion guide. Unlike the RF multipole, the stacked ring guide is an electrostatic ion guide and does not require an RF voltage source. The stacked ring guide imparts an axial acceleration by stepping the voltage down from one ring to another. However, the stacked ring guide provides little or no focusing, requires very fine spacing of many electrodes and requires many voltage sources or values to achieve simultaneous confinement and acceleration of the ions. In addition, the stacked ring guide is sensitive to the axial energy of the ions entering the guide and is known to suffer from axial trapping of ions.
FIG. 3 illustrates yet another alternative to the RF multipole ion guide known as a conventional ion funnel. The ion funnel is an improvement on the ring guide and provides some focusing. See, for example, Shaffer et al., xe2x80x9cAn Ion Funnel Interface for Improved Ion Focusing and Sensitivity Using Electrospray Ionization Mass Spectrometryxe2x80x9d, Anal. Chem., 70 (1998) 4111-4119, and Shaffer et al, PCT WO 97/49111. However, the ion funnel generally requires even more electrodes and voltages, including RF voltages. Moreover, the ion funnel traditionally has trouble transmitting low mass ions ( less than 200 AMU), severely limiting its usefulness for many mass spectrometry applications.
Thus, it would be advantageous to have an ion guide device and method that combine the benefits of the many conventional ion guides and techniques but do not have all the disadvantages associated with the conventional ion guides and techniques. Such an ion guide device and method would transport the analyte ions without significant loss through its ability to confine the ion beam. Further, such an ion guide and method would maintain some minimal level of axial velocity of the analyte ions through its ability to accelerate the ions by way of an axially oriented potential gradient. Such a device and method would not only have wide applicability but could be lower in cost and higher in reliability than conventional ion guides and methods.
The present invention provides a novel ion transport apparatus and method that can be used in mass spectrometry. The ion transport apparatus and method comprise a ring stack that extends inside a multipole. The apparatus and method achieve the focusing and confinement advantages of a conventional RF multipole and the advantage of an axial field of a conventional stacked ring guide or ion funnel. However, since the ring stack of the present invention is not used to establish a confining, effective-potential well, the ring spacing of the present apparatus can be greater than that of a conventional ring guide or ion funnel. As a result, the number of electrodes or rings and the corresponding number of voltages needed are reduced compared to the conventional ring guides. In addition, no RF is required on the rings in contrast to the ion funnel.
In one aspect of the invention, a ring pole ion guide apparatus is provided that comprises a multipole portion and a ring stack portion, wherein the ring stack portion extends inside the multipole portion. For the purposes of this invention, the ring pole ion guide apparatus is also referred to herein as the xe2x80x9cring polexe2x80x9d device, apparatus or guide to distinguish it from the conventional ring stack devices and the RF multipole devices.
In another aspect of the invention, a method of transporting ions using the ring pole ion guide apparatus described above is provided. After the ions are introduced into the input end of the ion guide, the method of transporting ions comprises the steps of focusing the ions by applying an RF field with the multipole portion, and accelerating the ions by applying a DC electric field with the ring stack portion. The ions are ejected from an output end.
In still another aspect of the invention, a mass spectrometer system is provided that utilizes the ring pole ion guide apparatus and method described above instead of conventional ion guides and techniques. The mass spectrometer system of the invention comprises the conventional components of a mass spectrometer system, such as an ion source, a mass analyzer, an ion detector system, and further comprises the ring pole ion guide apparatus of the present invention.
In another aspect of the invention, the ring pole ion guide apparatus is made longer to traverse several pressure transition stages in the mass spectrometer system. Several of the rings on the ring pole apparatus act as pressure partitions between adjacent pressure stages.
In still another aspect of the invention, the ring pole ion guide apparatus may be used in a collision cell or a system for dissociating ions. When used in the ion dissociation system of the present invention, the ring pole ion guide provides improved performance compared to conventional ion guides.